In meeting the goals and objectives of FMIC, the center continues to: -Service and maintain state-of-the-art equipment for unlimited access by intramural scientists. -Provide investigator training in the use and analysis of fluorescence and optical-based techniques. -Develop and optimize experimental protocols in collaboration with intramural scientists. -Maintain and develop state-of-the-art analysis tools and protocols in collaboration with investigators -Monitor and incorporate emerging fluorescence and optical technologies that will support the mission of NIEHS into FMIC. During this fiscal year, FMIC has collaborated and supported 50 Principle Investigators from all 5 programs within the NIEHS DIR. Some publications from this FY resulting from work in the center is listed in the bibliography below: Bibliography Bhattacharjee, S., Chatterjee, S., Jiang, J., Sinha, B.K., and Mason, R.P. (2012). Detection and imaging of the free radical DNA in cells--site-specific radical formation induced by Fenton chemistry and its repair in cellular DNA as seen by electron spin resonance, immuno-spin trapping and confocal microscopy. Nucleic acids research 40, 5477-5486. Cannon, R.E., Peart, J.C., Hawkins, B.T., Campos, C.R., and Miller, D.S. (2012). Targeting blood-brain barrier sphingolipid signaling reduces basal P-glycoprotein activity and improves drug delivery to the brain. Proceedings of the National Academy of Sciences of the United States of America 109, 15930-15935. Cartwright, T.A., Campos, C.R., Cannon, R.E., and Miller, D.S. (2013). Mrp1 is essential for sphingolipid signaling to p-glycoprotein in mouse blood-brain and blood-spinal cord barriers. J Cereb Blood Flow Metab 33, 381-388. Charoenpanich, A., Wall, M.E., Tucker, C.J., Andrews, D.M., Lalush, D.S., Dirschl, D.R., and Loboa, E. (2013). Cyclic Tensile Strain Enhances Osteogenesis and Angiogenesis in Human Mesenchymal Stem Cells from Osteoporotic Donors. Tissue Eng Part A. Das, S., Kumar, A., Seth, R.K., Tokar, E.J., Kadiiska, M.B., Waalkes, M.P., Mason, R.P., and Chatterjee, S. (2013). Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity. Toxicol Appl Pharmacol 269, 297-306. Ehrenshaft, M., Roberts, J.E., and Mason, R.P. (2013). Hypericin-mediated photooxidative damage of alpha-crystallin in human lens epithelial cells. Free Radic Biol Med 60, 347-354. Gao, H.M., Zhou, H., and Hong, J.S. (2012). NADPH oxidases: novel therapeutic targets for neurodegenerative diseases. Trends Pharmacol Sci 33, 295-303. Gassman, N.R., Stefanick, D.F., Kedar, P.S., Horton, J.K., and Wilson, S.H. (2012). Hyperactivation of PARP triggers nonhomologous end-joining in repair-deficient mouse fibroblasts. PLoS One 7, e49301. Gokhale, N.A., Zaremba, A., Janoshazi, A.K., Weaver, J.D., and Shears, S.B. (2013). PPIP5K1 modulates ligand competition between diphosphoinositol polyphosphates and PtdIns(3,4,5)P3 for polyphosphoinositide-binding domains. The Biochemical journal 453, 413-426. Gu, Z., Lamb, P.W., and Yakel, J.L. (2012). Cholinergic coordination of presynaptic and postsynaptic activity induces timing-dependent hippocampal synaptic plasticity. J Neurosci 32, 12337-12348. Guo, X., Kesimer, M., Tolun, G., Zheng, X., Xu, Q., Lu, J., Sheehan, J.K., Griffith, J.D., and Li, X. (2012). The NAD(+)-dependent protein deacetylase activity of SIRT1 is regulated by its oligomeric status. Scientific reports 2, 640. Horton, J.K., Stefanick, D.F., Gassman, N.R., Williams, J.G., Gabel, S.A., Cuneo, M.J., Prasad, R., Kedar, P.S., Derose, E.F., Hou, E.W., et al. (2013). Preventing oxidation of cellular XRCC1 affects PARP-mediated DNA damage responses. DNA repair 12, 774-785. Kang, H.S., Liao, G., DeGraff, L.M., Gerrish, K., Bortner, C.D., Garantziotis, S., and Jetten, A.M. (2013). CD44 plays a critical role in regulating diet-induced adipose inflammation, hepatic steatosis, and insulin resistance. PLoS One 8, e58417. Kojima, H., Muromoto, R., Takahashi, M., Takeuchi, S., Takeda, Y., Jetten, A.M., and Matsuda, T. (2012). Inhibitory effects of azole-type fungicides on interleukin-17 gene expression via retinoic acid receptor-related orphan receptors alpha and gamma. Toxicol Appl Pharmacol 259, 338-345. Li, H., Edin, M.L., Bradbury, J.A., Graves, J.P., DeGraff, L.M., Gruzdev, A., Cheng, J., Dackor, R.T., Wang, P.M., Bortner, C.D., et al. (2013). Cyclooxygenase-2 inhibits T helper cell type 9 differentiation during allergic lung inflammation via down-regulation of IL-17RB. American journal of respiratory and critical care medicine 187, 812-822. Lichti-Kaiser, K., ZeRuth, G., Kang, H.S., Vasanth, S., and Jetten, A.M. (2012). Gli-similar proteins: their mechanisms of action, physiological functions, and roles in disease. Vitam Horm 88, 141-171. Muessel, M.J., Harry, G.J., Armstrong, D.L., and Storey, N.M. (2013). SDF-1alpha and LPA modulate microglia potassium channels through rho gtpases to regulate cell morphology. Glia 61, 1620-1628. Numaga-Tomita, T., and Putney, J.W. (2013). Role of STIM1- and Orai1-mediated Ca2+ entry in Ca2+-induced epidermal keratinocyte differentiation. J Cell Sci 126, 605-612. Putney, J.W. (2013). Alternative Forms of the Store-Operated Calcium Entry Mediators, STIM1 and Orai1. Current topics in membranes 71, 109-123. Ren, R., Oakley, R.H., Cruz-Topete, D., and Cidlowski, J.A. (2012). Dual role for glucocorticoids in cardiomyocyte hypertrophy and apoptosis. Endocrinology 153, 5346-5360. Richter, K., Burch, L., Chao, F., Henke, D., Jiang, C., Daly, J., Zhao, M.L., Kissling, G., and Diaz, M. (2012). Altered pattern of immunoglobulin hypermutation in mice deficient in Slip-GC protein. J Biol Chem 287, 31856-31865. Robertson, S.D., Plummer, N.W., de Marchena, J., and Jensen, P. (2013). Developmental origins of central norepinephrine neuron diversity. Nat Neurosci 16, 1016-1023. Singh, A.P., Cummings, C.A., Mishina, Y., and Archer, T.K. (2013). SOX8 regulates permeability of the blood-testes barrier that affects adult male fertility in the mouse. Biol Reprod 88, 133. Srimaroeng, C., Cecile, J.P., Walden, R., and Pritchard, J.B. (2013). Regulation of renal organic anion transporter 3 (SLC22A8) expression and function by the integrity of lipid raft domains and their associated cytoskeleton. Cell Physiol Biochem 31, 565-578. Winuthayanon, W., Piyachaturawat, P., Suksamrarn, A., Burns, K.A., Arao, Y., Hewitt, S.C., Pedersen, L.C., and Korach, K.S. (2013). The natural estrogenic compound diarylheptanoid (D3): in vitro mechanisms of action and in vivo uterine responses via estrogen receptor alpha. Environ Health Perspect 121, 433-439, 439e431-435. Zhou, H., Liao, J., Aloor, J., Nie, H., Wilson, B.C., Fessler, M.B., Gao, H.M., and Hong, J.S. (2013). CD11b/CD18 (Mac-1) is a novel surface receptor for extracellular double-stranded RNA to mediate cellular inflammatory responses. J Immunol 190, 115-125.